This project deals with the interactions between EBV-infected cells and the host immune system in normal and immunodefective persons. For an improved understanding of this complex system, it is necessary to broaden our knowledge both on the interaction of the virus with different host cells in vitro and in vivo, and on the interplay between the virally infected cells and the host. This project aims at the analysis of certain questions at both levels, in a mutually interrelated way. The project consists of the following parts: I. Analysis of the virus-cell-host system II. Clinically related studies. Part I will deal with: 1. Continued study of the six proteins now known to be associated with EBV-transformed B cells, EBNA-1-5 and LMP; 2. Phenotype related differences between LCL and BL subtypes and role of such differences for identifying the tumor precursor cell of origin, and for target cell sensitivity to MHC- restricted cytotoxic T-cells; 3. Effector mechanisms mediating immune surveillance against EBV transformed cells; 4. Some aspects of the EBV-B cell interaction. Part III will focus on: 1. Methodological developments aimed at the demonstration of latently EBV-infected cells in vivo; 2. Identification and characterization of EBV carrying B-cells in vivo; 3. Effector mobilization during acute mononucleosis, compared to silent seroconversion; 4. EBV specific and non specific effector analysis in immunodefectives that can or cannot control the proliferaton of latently EBV-infected B-cells; 5. Host- EBV-B cell relationships in patients with AIDS or AIDS-related complex (ARC); 6. Antigen expression studies in nasopharyngeal carcinoma.